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Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease

Author

Listed:
  • Lanyu Zhang

    (University of Miami)

  • Tiago C. Silva

    (University of Miami)

  • Juan I. Young

    (University of Miami
    University of Miami)

  • Lissette Gomez

    (University of Miami)

  • Michael A. Schmidt

    (University of Miami
    University of Miami)

  • Kara L. Hamilton-Nelson

    (University of Miami)

  • Brian W. Kunkle

    (University of Miami
    University of Miami)

  • Xi Chen

    (University of Miami
    University of Miami)

  • Eden R. Martin

    (University of Miami
    University of Miami)

  • Lily Wang

    (University of Miami
    University of Miami
    University of Miami
    University of Miami)

Abstract

DNA methylation differences in Alzheimer’s disease (AD) have been reported. Here, we conducted a meta-analysis of more than 1000 prefrontal cortex brain samples to prioritize the most consistent methylation differences in multiple cohorts. Using a uniform analysis pipeline, we identified 3751 CpGs and 119 differentially methylated regions (DMRs) significantly associated with Braak stage. Our analysis identified differentially methylated genes such as MAMSTR, AGAP2, and AZU1. The most significant DMR identified is located on the MAMSTR gene, which encodes a cofactor that stimulates MEF2C. Notably, MEF2C cooperates with another transcription factor, PU.1, a central hub in the AD gene network. Our enrichment analysis highlighted the potential roles of the immune system and polycomb repressive complex 2 in pathological AD. These results may help facilitate future mechanistic and biomarker discovery studies in AD.

Suggested Citation

  • Lanyu Zhang & Tiago C. Silva & Juan I. Young & Lissette Gomez & Michael A. Schmidt & Kara L. Hamilton-Nelson & Brian W. Kunkle & Xi Chen & Eden R. Martin & Lily Wang, 2020. "Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer’s disease," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19791-w
    DOI: 10.1038/s41467-020-19791-w
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    Cited by:

    1. Lasse Pihlstrøm & Gemma Shireby & Hanneke Geut & Sandra Pilar Henriksen & Annemieke J. M. Rozemuller & Jon-Anders Tunold & Eilis Hannon & Paul Francis & Alan J. Thomas & Seth Love & Jonathan Mill & Wi, 2022. "Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Tiago C. Silva & Juan I. Young & Lanyu Zhang & Lissette Gomez & Michael A. Schmidt & Achintya Varma & X. Steven Chen & Eden R. Martin & Lily Wang, 2022. "Cross-tissue analysis of blood and brain epigenome-wide association studies in Alzheimer’s disease," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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